Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating factor in patients with chemotherapy-related febrile neutropenia.

Abstract

Purpose: To determine whether granulocyte-macro phage colony-stimulating factor (GM-CSF) used in addi tion to standard inpatient antibiotic therapy shortens the period of hospitalization due to chemotherapy-induced neutropenic fever.Patients and Methods: One hundred thirty-four pa tients with aliem atologic (n = 47) or solid tumor (n = 87) who had severe neutropenia {< 0.5 x 10 9/L) and fever (> 38.5°C once or > 38°C twice over a 12-hour observation period) w ere randomly assigned to receive GM-CSF 5 /u g /k g /d (n = 65) or placebo (n -69) in con junction with broad-spectrum antibiotics for a minimum of 4 days and a maximum of 14 days* GM-CSF/placebo and antibiotics were stopped if the neutrophil count was greater than 1.0 x 109/L and temperature less than 37.5°C during 2 consecutive days, or for a leukocyte count > 1 0 x 1 09/lv both followed by a 24-hour observa tion period (hospitalization period).Results: Compared with placebo, GM-CSF enhanced neutrophil recovery. Median neutrophil counts at day 4 w ere 2.5 x 109/L (range, 0 to 25) in the GM-CSF arm and 1.3 x 109/L (range, 0 to 9) in the placebo arm (P < .001). No significant difference was observed with re gard to median number of days w ith less than 1.0 x 10 9/ L neutrophils (4 v 4 ) or days of fever {3 v3). The median number of days patients w ere hospitalized while on study was comparable in the GM-CSF and placebo groups at 6 (range, 3 to 14) versus 7 (range/ 4 to 14), respectively, according to an intention-to-treat analysis (P = .27). Q uality-of-life scores in 90 patients demon strated significant differences in favo r of the placebo group. Hospital costs w ere significantly higher for GM -CSF -treated patients if GM-CSF w as included in the price (median costs, $ 4 ,1 4 0 [US] for GM-CSF v $ 5 9 0 for p la cebo; P < .05).Conclusion: These results indicate that GM-CSF does not affect the number of days for resolution of fever or the hospitalization period for this patient group, a l though a significant effect of GM-CSF w as observed on neutrophil recovery.J Clin Oncol 1 4 :6 1 9 *6 2 7 , © 1 9 9 6 b y American So ciety o f Clinical Oncology. C HEMOTHERAPY-RELATED neutropenia and fever is a complication that occurs frequently during treatment of cancer patients. In particular, the severity and duration of neutropenia determines the risk of infec tion and the outcome of the patient.1, 2 Recently, different hematopoietic growth factors (HGFs) have been pro duced, which allows the opportunity to modulate the pe riod of granulocytopenia.Two options are available for applying HGFs after standard chemotherapy.3 First, HGF can be given as an adjunct to chemotherapy until recovery of peripheralblood counts is noted, in a number of studies, this policy has resulted in a 50% reduction of infectious complications,4,5 while in other studies, no significant effect has been shown with regard to the incidence of bacteremia, days of fever, or hospitalization duration.ü,; A second possibility would be to apply HGF only in the case of infection.8"n This approach woul...

Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitus

“…Many common infections have been shown to be more frequent in patients with diabetes, including community-acquired pneumonia, urinary tract infection and soft-tissue infection. [37][38][39] Similar to the patients with diabetes, obese individuals have been reported to display an increased susceptibility to the same types of common infection. 15 Because central obesity, insulin resistance and diabetes are components of the metabolic syndrome, one may speculate that similar pathophysiological mechanisms are responsible for the increased susceptibility to infections in both these two clinical conditions.…”

Penggunaan Granulocyte Colony-Stimulating Factor pada Pasien Tumor Padat yang Mengalami Neutropenia

“…Hasil penelitian menunjukkan durasi neutropenia, perawatan, dan pemberian antibiotik yang lebih singkat pada kelompok pasien yang mendapat GM-CSF (p<0,05), namun tidak terdapat perbedaan yang bermakna dalam lama demam (level of evidence: 1b). Hasil studi ini tidak sama dengan hasil penelitian yang dilakukan oleh Vellenga E dkk 12 yang juga menggunakan GM-CSF pada 134 pasien kanker dengan demam (suhu >38°C) dan neutropenia (ANC<500/μL). Setelah dilakukan randomisasi, 65 pasien mendapat GM-CSF dosis 5μg/kg dengan median lama pemberian 5 hari.…”

Update on the Management of Febrile Neutropenia

“…They may be helpful in documented infections not responding to appropriate treatment, in severe uncontrolled fungal infections and in lifethreatening infections such as pneumonia and soft tissue infections, in patients in whom severe neutropenia (<0.1 x 10 9 /l) is expected to persist for more than five to seven days. [55][56][57] Trials are required to evaluate their effectiveness and define the optimal schedule of administration.…”